1. Field of the Invention
The invention relates to apparatus and methods for determining tissue characteristics of, for example, a human or animal.
2. Background of the Related Art
Spectroscopic methods for determining tissue characteristics are known and have been widely used to interrogate changes in tissue. A number of these distinct spectroscopic techniques are available that provide specific information depending on the nature of the interaction of light with cells and the natural chromophores present in tissue. These interactions include the absorption of light at a particular wavelength, the reemission of absorbed light as fluorescence, the scattering (redirection) of light at a particular wavelength and the change in polarization between the absorbed or scattered light and the reemitted light.
For example, it is known to irradiate a target tissue with electromagnetic radiation and to detect returned electromagnetic radiation to determine characteristics of the target tissue. In known methods, the amplitudes and wavelengths of the returned radiation are analyzed to determine characteristics of the target tissue. For instance, U.S. Pat. No. 4,718,417 to Kittrell et al. discloses a method for diagnosing the type of tissue within an artery, wherein a catheter is inserted into an artery and excitation light at particular wavelengths is used to illuminate the interior wall of the artery. Material or tissue within the artery wall emits fluorescent radiation in response to the excitation light. A detector detects the fluorescent radiation and analyzes the amplitudes and wavelengths of the emitted fluorescent radiation to determine whether the illuminated portion of the artery wall is normal, or covered with plaque. The contents of U.S. Pat. No. 4,718,417 are hereby incorporated by reference.
U.S. Pat. No. 4,930,516 to Alfano et al. discloses a method for detecting cancerous tissue, wherein a tissue sample is illuminated with excitation light at a first wavelength, and fluorescent radiation emitted in response to the excitation light is detected. The wavelength and amplitude of the emitted fluorescent radiation are then examined to determine whether the tissue sample is cancerous or normal. Normal tissue will typically have amplitude peaks at certain known wavelengths, whereas cancerous tissue will have amplitude peaks at different wavelengths. Alternatively the spectral amplitude of normal tissue will differ from cancerous tissue at the same wavelength. The disclosure of U.S. Pat. No. 4,930,516 is hereby incorporated by reference. The above described methods are referred to as fluorescence spectroscopy.
Still other patents, such as U.S. Pat. No. 5,369,496 to Alfano et al., disclose methods for determining characteristics of biological materials, wherein a target tissue is illuminated with light, and backscattered or reflected light is analyzed to determine the tissue characteristics. The contents of U.S. Pat. No. 5,369,496 are hereby incorporated by reference. This type of method is referred to as absorption spectroscopy.
It is also known to look at the decay time of fluorescent emissions to determine the type or condition of an illuminated tissue. These methods are referred to as time resolved spectroscopy. Generally, apparatus for detection of the lifetime of fluorescent emissions have concentrated on directly measuring the lifetime of the fluorescent emissions. Typically, a very short burst of excitation light is directed at a target tissue, and fluorescent emissions from the target tissue are then sensed with a detector. The amplitude of the fluorescent emissions are recorded, over time, as the fluorescent emissions decay. The fluorescent emissions may be sensed at specific wavelengths, or over a range of wavelengths. The amplitude decay profile, as a function of time, is then examined to determine a property or condition of the target tissue.
For instance, U.S. Pat. No. 5,562,100 to Kittrell et al. discloses a method of determining tissue characteristics that includes illuminating a target tissue with a short pulse of excitation radiation at a particular wavelength, and detecting fluorescent radiation emitted by the target tissue in response to the excitation radiation. In this method, the amplitude of the emitted radiation is recorded, over time, as the emission decays. The amplitude profile is then used to determine characteristics of the target tissue. Similarly, U.S. Pat. No. 5,467,767 to Alfano et al. also discloses a method of determining whether a tissue sample includes cancerous cells, wherein the amplitude decay profile of fluorescent emissions are examined. The contents of U.S. Pat. Nos. 5,562,100 and 5,467,767 are hereby incorporated by reference.
Other U.S. patents have explained that the decay time of fluorescent emissions can be indirectly measured utilizing phase shift or polarization anisotropy measurements. For instance, U.S. Pat. No. 5,624,847 to Lakowicz et al. discloses a method for determining the presence or concentration of various substances using a phase shift method. U.S. Pat. No. 5,515,864 to Zuckerman discloses a method for measuring the concentration of oxygen in blood utilizing a polarization anisotropy measurement technique. Each of these methods indirectly measure the lifetime of fluorescent emissions generated in response to excitation radiation. The contents of U.S. Pat. Nos. 5,624,847 and 5,515,864 are hereby incorporated by reference.
None of the prior art methods discussed above alone is sufficient to accurately measure changes in tissue characteristics. That is, as more fully discussed below, as tissue undergoes changes from normal to, for example, cancerous tissue, fluorescence spectroscopy becomes less effective in determining tissue characteristics because it is less sensitive to the morphological changes occurring, as compared to absorption spectroscopy. Likewise, absorption spectroscopy alone is insufficient to assess changes in tissue characteristics because it is less sensitive to biochemical changes in tissue, as compared to fluorescence spectroscopy.
It is known to combine two or more measurement techniques to arrive at a more accurate ultimate determination. For example, U.S. Pat. No. 5,582,168 to Samuels et al., the contents of which are hereby incorporated by reference, discloses an apparatus and method for detecting changes in the lens of an eye. Samuels et al. teach measuring both transmission or Raman or fluorescence emission, as well as scattering, reflection or similar effects. The material under examination is then normalized using a ratio of the fluorescence emission intensity to the scattering or reflected intensity. However, while this method addresses biochemical changes due to disease, it does not address morphological changes due to disease.
Further, generally, prior art spectroscopic methods focus on tissue characteristics at a single point or minium number of points on the tissue. Taking measurements at just one point or a minimum number of points can be misleading as it does not provide a sufficient sampling of tissue area to accurately reflect the tissue's condition.